In the past year we have used radiolabeled phospholipid precursors to measure the subcellular synthesis, processing and secretion as surfactant of saturated phosphatidylcholine and other surfactant related lipids in newborn lambs. A technique for mulitple sampling of surfactant in vivo was used to measure radiolabeled surfactant secretion and biological half-life in newborn and adult sheep. These studies form the basis for proposed work in premature lambs. We have a premature lamb newborn nursery that allows us to study these animals as chronic preparations. We will complete our studies of the labeling of endogenously synthesized surfactant in 120-day premature lambs using (14C) palmitic acid and as a phospholipid precursor. Simultaneously, the metabolism of exogenously administered surfactant will be traced by using radiolabeled natural surfactant for treatment of RDS. The optimal dose of natural surfactant replacement therapy will be defined in relation to duration of the effectiveness of therapy and the extent of reversal of respiratory failure. Our studies will include animals at 120, 130 and 140 days gestational age. We also will begin to use the chronically catheterized fetal lamb at 120 days to define fetal surfactant metabolism, again using radiolabeled phospholipid precursors to study surfactnat secretion.